Thesis Title

Author

Date of Graduation

Degree

Department

Biomedical Sciences

Committee Chair

R. Tyler Morris

Keywords

adiponectin, colitis, TNF-a, TACE, inflammation, adipokine

Subject Categories

Medical Molecular Biology

Abstract

Inflammation plays a key role in the clinical manifestation of disease. For example, inflammatory bowel disease elevates the expression of pro-inflammatory cytokines in the colon. However, the role of neighboring mesenteric fat depots during colitis and impact on expression of the adiponectin remain unclear. This study tested the hypothesis that colitis causes a dysregulation of adiponectin expression through a TNF-a dependent pathway. Colitis was induced in BALB/c mice through use of 5% dextran sulfate sodium (DSS). Then mice (n=5-6) were subjected to twice daily intraperitoneal injections of a TNF-α converting enzyme (TACE) inhibitor, DPC-333. Body weight, bleeding, and stool consistency were evaluated twice daily for Disease Activity Index (DAI). Treatment with DPC-333 was observed to significantly reduced DAI on day 7. Contrary to the hypothesis, the expression of TNF-a, adiponectin, and MCP-1 in mesenteric adipose tissue did not change in response to colitis. Interestingly, plasma adiponectin concentration increased during colitis, suggesting adiponectin secretion from of an alternative tissue, such as brown adipose. In conclusion, adiponectin protein expression from neighboring mesenteric fat does not appear to change in response to murine colitis.